tbuckley/cabot-search huggingface dataset:
Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses
Authors: Torgny Karlsson, Fatemeh Hadizadeh, Mathias Rask‐Andersen, Åsa Johansson, Weronica E. Ek
Journal: Arthritis & Rheumatology (2023)

Objective Although the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proven. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing 5 different rheumatic diseases. Methods Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex‐specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for 5 rheumatic diseases: rheumatoid arthritis (n = 8,381 cases), osteoarthritis (n = 87,430), psoriatic arthropathy (n = 933), gout (n = 13,638), and inflammatory spondylitis (n = 4,328). Results Using linear MR, we found that 1 SD increase in BMI increases the incidence rate for rheumatoid arthritis (incidence rate ratio [IRR] 1.52 [95% confidence interval (95% CI) 1.36–1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43–1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31–2.48]), gout (IRR 1.73 [95% CI 1.56–1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14–1.57]) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy ( P for sex interaction = 3.3 × 10 −4 ) and gout ( P for sex interaction = 4.3 × 10 −3 ), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women ( P = 1.8 × 10 −3 ). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women ( P = 0.03). Conclusion Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex‐ and BMI‐specific causal effects identified here provide further insight into rheumatic disease etiology and mark an important step toward personalized medicine.
“Humanity’s Debt to Medical Science”
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Smallpox in 1922
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation in Persistent AF
Authors: Sanghamitra Mohanty, Prasant Mohanty, Andrea Natale
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults
Authors: Taraz Samandari, Joshua B. Ongalo, Kimberly D. McCarthy, Richard K. Biegon, Philister A. Madiega, Anne Mithika, Joseph Orinda, Grace M. Mboya, Patrick Mwaura, Omu Anzala, Clayton Onyango, Fredrick O. Oluoch, Eric Osoro, Charles-Antoine Dutertre, Nicole Tan, Shou Kit Hang, Smrithi Hariharaputran, David C. Lye, Amy Herman-Roloff, Nina Le Bert, Antonio Bertoletti
Journal: Journal of Clinical Investigation (2023)

BackgroundSARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2-specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.MethodsWe collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.ResultsAmong asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.ConclusionsThe high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2-specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.FundingUS Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health's National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).
Bilingual Care in Clinical Trials—Understanding the Need for Expanded Research in Latino Communities
Authors: Parker Entrup, Stephanie Garcia, O. Trent Hall
Journal: JAMA Network Open (2023)

Federico E. Vaca, MD, MPH; James Dziura, PhD; Fuad Abujarad, PhD; Michael Pantalon, PhD; Allen Hsiao, MD; Jesse Reynolds, MS; Kaitlin R. Maciejewski, MS; Craig A. Field, PhD; Gail D'Onofrio, MD
Intrinsically bioactive and biomimetic nanoparticle-derived therapies alleviate asthma by regulating multiple pathological cells
Authors: Jiajun Cai, Hui Tao, Huan Liu, Yi Hu, Songling Han, Wendan Pu, Lanlan Li, Gang Li, Chenwen Li, Jianxiang Zhang
Journal: Bioactive Materials (2023)

Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma
Authors: Benedetta Apollonio, Filomena Spada, Nedyalko Petrov, Domenico Cozzetto, Despoina Papazoglou, Peter Jarvis, Shichina Kannambath, Manuela Terranova-Barberio, Rose-Marie Amini, Gunilla Enblad, Charlotte Graham, Reuben Benjamin, Elisabeth Phillips, Richard Ellis, Rosamond Nuamah, Mansoor Saqi, Dinis P. Calado, Richard Rosenquist, Lesley A. Sutton, Jon Salisbury, Georgios Zacharioudakis, Anna Vardi, Patrick R. Hagner, Anita K. Gandhi, Marina Bacac, Christina Claus, Pablo Umana, Ruth F. Jarrett, Christian Klein, Alexander Deutsch, Alan G. Ramsay
Journal: Journal of Clinical Investigation (2023)

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of lymph node (LN) fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identify the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network, expressing elevated fibroblast activated protein (FAP). RNA-sequencing analyses reveal that exposure to DLBCL reprograms key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen presentation molecules. Functional assays show that DLBCL-activated FRCs (DLBCL-FRCs) hinder optimal TIL and chimeric antigen receptor T cell (CAR-T) migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrate the potential to target inhibitory FRCs to rejuvenate interacting TILs. Co-treating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented anti-lymphoma TIL cytotoxicity. Together, our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis and optimizing immunotherapy for patients.
In Synergy: Optimizing CAR T Development and Personalizing Patient Care Using Single-Cell Technologies
Authors: Oren Barboy, Yonatan Katzenelenbogen, Rotem Shalita, Ido Amit
Journal: Cancer Discovery (2023)

Chimeric antigen receptor (CAR) T therapies hold immense promise to revolutionize cancer treatment. Nevertheless, key challenges, primarily in solid tumor settings, continue to hinder the application of this technology. Understanding CAR T-cell mechanism of action, in vivo activity, and clinical implications is essential for harnessing its full therapeutic potential. Single-cell genomics and cell engineering tools are becoming increasingly effective for the comprehensive research of complex biological systems. The convergence of these two technologies can accelerate CAR T-cell development. Here, we examine the potential of applying single-cell multiomics for the development of next-generation CAR T-cell therapies. Although CAR T-cell therapies have demonstrated remarkable clinical results in treating cancer, their effectiveness in most patients and tumor types remains limited. Single-cell technologies, which are transforming our understanding of molecular biology, provide new opportunities to overcome the challenges of CAR T-cell therapies. Given the potential of CAR T-cell therapy to tip the balance in the fight against cancer, it is important to understand how single-cell multiomic approaches can be leveraged to develop the next generations of more effective and less toxic CAR T-cell products and to provide powerful decision-making tools for clinicians to optimize treatment and improve patient outcomes.
Practice Patterns of Screening for Hydroxychloroquine Retinopathy in South Korea
Authors: Jiyeong Kim, Ko Eun Kim, Ji Hong Kim, Seong Joon Ahn
Journal: JAMA Network Open (2023)

Importance Practice patterns of hydroxychloroquine retinopathy screening have not yet been reported at a national level in South Korea. Objective To investigate the practice patterns of timing and modality for hydroxychloroquine retinopathy screening in South Korea. Design, Setting, and Participants This nationwide population-based cohort study of patients in South Korea used data from the national Health Insurance Review and Assessment database. Patients at risk were identified as those who had initiated hydroxychloroquine therapy between January 1, 2009, and December 31, 2020, and used it for 6 months or more. Patients were excluded if they underwent any of the 4 screening modalities recommended by the American Academy of Ophthalmology (AAO) for other ophthalmic diseases prior to hydroxychloroquine use. The timing and modalities of screening used in baseline and monitoring examinations were assessed between January 1, 2015, and December 31, 2021, among patients at risk and long-term (≥5 years) users. Exposure Adherence of baseline screening practices to the 2016 AAO recommendations (fundus examination within 1 year of drug use) was evaluated; adherence of monitoring examinations in year 5 was classified as appropriate (≥2 tests recommended by the AAO), unscreened (no test performed), and underscreened (insufficient number of tests). Main Outcomes and Measures Timing of screening and modalities used at baseline and monitoring examinations. Results A total of 65 406 patients at risk (mean [SD] age, 53.0 [15.5] years; 50 622 women [77.4%]) were included; 29 776 patients were long-term users (mean [SD] age, 50.1 [14.7] years; 24 898 women [83.6%]). Baseline screening was performed for 20.8% of the patients within 1 year, with a gradual increase from 16.6% in 2015 to 25.6% in 2021. Monitoring examinations, mostly using optical coherence tomography and/or visual field tests, were performed for only 13.5% of the long-term users in year 5 and for 31.6% of the long-term users after 5 years. Appropriate monitoring was performed for less than 10% of long-term users each year from 2015 to 2021; however, the percentage gradually increased over time. The percentage of patients undergoing any monitoring examination in year 5 was 2.3 times greater for those who had received baseline screening than for those who did not (27.4% vs 11.9%; P &amp;amp;lt; .001). Conclusions and Relevance This study suggests there is an improving trend in retinopathy screening among hydroxychloroquine users in South Korea; however, most long-term users remained unscreened after 5 years of use. Baseline screening may be useful in reducing the number of unscreened long-term users.
A strategy of local hydrogen capture and catalytic hydrogenation for enhanced therapy of chronic liver diseases
Authors: Geru Tao, Feng Liu, Zhaokui Jin, Boyan Liu, Hao Wang, Daosheng Li, Wei Tang, Yuan Chen, Qianjun He, Shucun Qin
Journal: Theranostics (2023)

Background: Chronic liver diseases (CLD) frequently derive from hepatic steatosis, inflammation and fibrosis, and become a leading inducement of cirrhosis and hepatocarcinoma.Molecular hydrogen (H2) is an emerging wide-spectrum anti-inflammatory molecule which is able to improve hepatic inflammation and metabolic dysfunction, and holds obvious advantages in biosafety over traditional anti-CLD drugs, but existing H2 administration routes cannot realize the liver-targeted high-dose delivery of H2, severely limiting its anti-CLD efficacy.Method: In this work, a concept of local hydrogen capture and catalytic hydroxyl radical (•OH) hydrogenation is proposed for CLD treatment.The mild and moderate non-alcoholic steatohepatitis (NASH) model mice were intravenously injected with PdH nanoparticles firstly, and then daily inhaled 4% hydrogen gas for 3 h throughout the whole treatment period.After the end of treatment, glutathione (GSH) was intramuscularly injected every day to assist the Pd excretion.Results: In vitro and in vivo proof-of-concept experiments have confirmed that Pd nanoparticles can accumulate in liver in a targeted manner post intravenous injection, and play a dual role of hydrogen captor and •OH filter to locally capture/store the liver-passing H2 during daily hydrogen gas inhalation and rapidly catalyze the •OH hydrogenation into H2O.The proposed therapy significantly improves the outcomes of hydrogen therapy in the prevention and treatment of NASH by exhibiting a wide range of bioactivity including the regulation of lipid metabolism and anti-inflammation.Pd can be mostly eliminated after the end of treatment under the assistance of GSH. Conclusion:Our study verified a catalytic strategy of combining PdH nanoparticles and hydrogen inhalation, which exhibited enhanced anti-inflammatory effect for CLD treatment.The proposed catalytic strategy will open a new window to realize safe and efficient CLD treatment.
Progress in Adrenal Cortical Neoplasms: From Predictive Histomorphology to FLCN-Driven Germline Pathogenesis and the Prognostic Performance of Multiparameter Scoring Systems in Pediatric Adrenal Cortical Neoplasms
Authors: Ozgur Mete, C. Christofer Juhlin
Journal: Endocrine Pathology (2023)
Induction of ER stress-mediated apoptosis through SOD1 upregulation by deficiency of CHI3L1 inhibits lung metastasis
Authors: Ji Eun Yu, In Jun Yeo, Seung Sik Yoo, Sung-hyun Kim, Dong Ju Son, Jaesuk Yun, Sang-Bae Han, Jin Tae Hong
Journal: Theranostics (2023)

Chitinase-3-like protein 1 (CHI3L1), which is secreted by immune and inflammatory cells, is associated with several inflammatory diseases.However, the basic cellular pathophysiological functions of CHI3L1 are not well characterized.To investigate the novel pathophysiological function of CHI3L1, we performed LC-MS/MS analysis of cells transfected with Myc-vector and Myc-CHI3L1.We analyzed the changes in the protein distribution in Myc-CHI3L1 transfected-cells, and identified 451 differentially expressed proteins (DEPs) compared with Myc-vector-transfected-cells.The biological function of the 451 DEPs was analyzed and it was found that the proteins with endoplasmic reticulum (ER)-associated function were much more highly expressed in CHI3L1-overexpressing cells.We then compared and analyzed the effect of CHI3L1 on the ER chaperon levels in normal lung cells and cancer cells.We identified that CHI3L1 is localized in the ER.In normal cells, the depletion of CHI3L1 did not induce ER stress.However, the depletion of CHI3L1 induces ER stress and eventually activates the unfolded protein response, especially the activation of Protein kinase R-like endoplasmic reticulum kinase (PERK), which regulates protein synthesis in cancer cells.CHI3L1 may not affect ER stress owing to the lack of misfolded proteins in normal cells, but instead activate ER stress as a defense mechanism only in cancer cells.Under ER stress conditions induced by the application of thapsigargin, the depletion of CHI3L1 induces ER stress through the upregulation of PERK and PERK downstream factors (eIF2α and ATF4) in both normal and cancer cells.However, these signaling activations occur more often in cancer cells than in normal cells.The expression of Grp78 and PERK in the tissues of patients with lung cancer was higher compared with healthy tissues.It is well known that ER stress-mediated PERK-eIF2α-ATF4 signaling activation causes apoptotic cell death.ER stress-mediated apoptosis induced by the depletion of CHI3L1 occurs in cancer cells, but rarely occurs in normal cells.Consistent with results from the in vitro model, ER stress-mediated apoptosis was greatly increased during tumor growth and in the lung metastatic tissue of CHI3L1-knockout (KO) mice.The analysis of "big data" identified superoxide dismutase-1 (SOD1) as a novel target of CHI3L1 and interacted with CHI3L1.The depletion of CHI3L1 increased SOD1 expression, resulting in ER stress.Furthermore, the depletion of SOD1 reduced the expression of ER chaperones and ER-mediated apoptotic marker proteins, as well as apoptotic cell death induced by the depletion of CHI3L1 in in vivo and in vitro models.These results suggest that the depletion of CHI3L1 increases ER stress-mediated apoptotic cell death through SOD1 expression, and subsequently inhibits lung metastasis.